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Background: Respiratory dysfunction is an important contributor to morbidity and mortality in advanced Parkinson's disease (PD), but it is unclear what parameters are sensitive to diagnose and monitor respiratory dysfunction across disease phases. Objectives: We aimed to characterize respiratory dysfunction in mild to moderate PD. Methods: In 20 individuals without cardiopulmonary comorbidity, pulmonary and inspiratory muscle function testing were performed ON‐medication. Subsequently, the acute ventilatory response to hypoxia (HVR) was assessed by gradually decreasing FIO2 from 0.209 (room air) to 0.127, which was compared to eight age‐ and sex‐matched healthy controls under arterial blood gas monitoring. Lastly, on different days, the same 20 individuals with PD underwent six blinded exposures to 45‐min normobaric hypoxia at FiO2 0.163 and 0.127 or placebo OFF‐medication to assess breathing responses. Results: At rest, individuals with greatest PD severity had a lower tidal volume (pairwise comparisons: 0.59 vs. 0.74, P = 0.038–0.050) and tended to have a higher breathing frequency (17.7 vs. 14.4, P = 0.076), despite normal pulmonary function. A 45‐min exposure to hypoxia induced a significantly lower acute HVR in individuals with PD compared to controls (−0.0489 vs. 0.133 L.min/%, P = 0.0038). Acute HVR was reduced regardless of disease severity. Subacute HVR in individuals with milder disease tended to be higher compared to those with more advanced disease (P = 0.079). Conclusions: Respiratory dysfunction is present in individuals with PD, including those with relatively mild disease severity, and is characterized by altered breathing patterns at rest, as well as a lower HVR, despite normal pulmonary and inspiratory muscle function testing. [ABSTRACT FROM AUTHOR]

This research evaluated the protective role of a combined extract of Dioscorea bulbifera and Zingiber officinale (DBZO) against respiratory dysfunction caused by particulate matter (PM2.5) exposure in BALB/c mice. The bioactive compounds identified in the DBZO are catechin, astragalin, 6-gingerol, 8-gingerol, and 6-shogaol. DBZO ameliorated cell viability and reactive oxygen species (ROS) production in PM2.5-stimulated A549 and RPMI 2650 cells. In addition, it significantly alleviated respiratory dysfunction in BALB/c mice exposed to PM2.5. DBZO improved the antioxidant systems in lung tissues by modulating malondialdehyde (MDA) content, as well as levels of reduced glutathione (GSH) and superoxide dismutase (SOD). Likewise, DBZO restored mitochondrial dysfunction by improving ROS levels, mitochondrial membrane potential, and ATP production. Moreover, DBZO modulated the levels of neutrophils, eosinophils, monocytes, and lymphocytes (specifically CD4+, CD8+, and CD4+IL-4+ T cells) in blood and IgE levels in serum. DBZO was shown to regulate the c-Jun N-terminal kinase (JNK) pathway, nuclear factor kappa B (NF-κB) pathway, and transforming growth factor β (TGF-β)/suppressor of mothers against decapentaplegic (Smad) pathway. Histopathological observation indicated that DBZO mitigates the increase in alveolar septal thickness. These findings indicate that DBZO is a promising natural agent for improving respiratory health. [ABSTRACT FROM AUTHOR]

Abstract Pneumonia after cervical spinal cord injury (CSCI) is a common and serious complication; however, its nutrition-related etiology has not yet been elucidated. This study aimed to elucidate the effects of nutritional factors on pneumonia after CSCI. Patients with acute traumatic CSCI who were admitted within 3 days after injury and followed up for at least 3 months were retrospectively examined. Occurrence of pneumonia, nutritional status, severity of dysphagia, vital capacity, use of respirators, and motor scores for paralysis were evaluated. Of 182 patients included in this study, 33 (18%) developed pneumonia. Multiple logistic regression analysis revealed that low nutritional status, severe paralysis, and low vital capacity were significant risk factors for pneumonia. The severity of paralysis, respiratory dysfunction, and poor nutritional status can affect the occurrence of pneumonia after CSCI. In addition to respiratory management, nutritional assessment and intervention may play key roles in preventing pneumonia associated with spinal cord injury-induced immune depression. Nutritional care should be provided as soon as possible when the nutritional status of a patient worsens after an injury.

Relevance. One of the most common complications after cardiac surgery is respiratory dysfunction (RD). The high-risk group includes patients after the left ventricle geometric reconstruction (LVGR) due to the presence of chronic heart failure, as well as the complexity and extent of the surgical intervention. At the moment, in clinical practice there is no uniform approach to predicting RD in patients in this group. The aim: to identify predictors of the development of RD in the early postoperative period in patients after LVGR. Materials and methods. The study included 54 patients who underwent LVGR surgery. Two groups of patients were identified: group I — patients without respiratory complications in the early postoperative period (n = 34); group II — patients with RD in the early period (n = 20). Cardiac function, respiratory system and gas exchange parameters were assessed in the pre- and early postoperative period. Results and Discussion. Echocardiography and spirometry indices in the group with RD were reduced before surgery relative to group I (FVC by 10.9 %, p = 0.009; EDV by 27 %, p = 0.004). Patients with RD on the first day after surgery were characterized by a pronounced disturbance in gas exchange compared to patients in group I (PaO2/FiO2 decreased by 45.1 %, p 0.001; Qs/Qt increased by 71.4 %, p 0.001). A multifactorial model was developed, which included three basic predictors of RD development: FVC, FEF50 and EDV. With a decrease in model indicators by 1 %, the risk of developing RD increased by 33.5 %, 24.8 % and decreased by 6.5 %, respectively. According to ROC-analysis, the most significant indicators were FEV3 (AUC 0.829 ± 0.079) and EDV (0.838 ± 0.087). To assess the risk of developing RD, a classification tree was constructed. Node 7 is characterized by the highest risk with the following parameters: FVC ≤ 89.5 %, EDV 173.2 ml, FEF50 ≤ 78.9 %. Conclusion. Impaired gas exchange on the first day after surgery was detected in all studied patients, however, pronounced RD was observed precisely in patients with the most reduced parameters of the cardiorespiratory system before surgery. The developed model for predicting RD in patients after LVGR makes it possible to assess the risk of respiratory complications at the surgical planning stage and prepare the patient’s cardiorespiratory system for the upcoming surgical intervention.

• In a large cohort of myasthenia gravis patients with mild respiratory symptoms and disability, portable respiratory function tests were useful to screen those at risk of deterioration. • MIP and SNIPs were good indicators of respiratory muscle weakness and MIP best correlated with measures of disability and quality of life. • Females had a higher likelihood of presenting with an abnormal FVC and MIP than males. Patients with myasthenia gravis (MG) can present with respiratory dysfunction, ranging from exercise intolerance to overt respiratory failure, increased fatigue, or sleep-disordered breathing. To investigate the value of multiple respiratory tests in MG, we performed clinical and respiratory assessments in patients with mild to moderate generalized disease. One-hundred and thirty-six patients completed the myasthenia gravis quality-of-life score(MG-QOL-15), myasthenia gravis impairment index(MGII), Epworth sleepiness scale(ESS), University of California-San Diego Shortness of Breath Questionnaire(UCSD-SOB), Modified Medical Research Council Dyspnea Scales(MRC-DS), supine and upright forced vital capacity(FVC), maximal inspiratory pressures(MIPs) and sniff nasal inspiratory pressures(SNIP). Seventy-three (54 %) had respiratory and/or bulbar symptoms and 45 (33 %) had baseline abnormal FVC, with no significant postural changes (p = 0.89); 55 (40.4 %) had abnormal MIPs and 50 (37 %) had abnormal SNIPs. Overall, there were low scores on respiratory and disability scales. Females had increased odds of presenting with abnormal FVC (OR 2.89, p = 0.01) and MIPs (OR 2.48, p = 0.022). There were significant correlations between MIPs, FVC and SNIPs; between MGII/MG-QOL15 and UCSD-SOB/MRC-DS and between ESS and respiratory scales in the whole group. Our data suggests that office-based respiratory measurements are a useful screening method for stable MG patients, even when presenting with minimal respiratory symptoms and no significant disability. [ABSTRACT FROM AUTHOR]

Background: GNE myopathy is an ultra-rare autosomal recessive distal myopathy caused by pathogenic variants of the GNE gene, which encodes a key enzyme in sialic acid biosynthesis. The present study aimed to examine the long-term progression of GNE myopathy, genotype–phenotype correlations, and complications to provide useful information for predicting patient progression and designing clinical trials using a large collection of registry data over a 10-year period. Methods: We analyzed 220 Japanese patients with GNE myopathy from a national registry in Japan. Diagnoses were confirmed by genetic curators based on genetic analysis reports. We analyzed registration sheets and annually updated items completed by attending physicians. Results: In total, 197 of 220 participants (89.5%) carried p.D207V or p.V603L in at least one allele. The median disease duration to loss of ambulation was estimated to be 10 years in p.V603L homozygotes (n = 48), whereas more than 90% of p.D207V/p.V603L compound heterozygotes were estimated to be ambulatory even 20 years after disease onset according to Kaplan–Meier analysis (p < 0.001). Moreover, participants with a younger age of onset lost ambulation earlier regardless of genotype. A decline in respiratory function was observed as the disease progressed, particularly in p.V603L homozygotes, whereas none of the p.D207V/p.V603L compound heterozygotes showed a decline. Conclusions: The present study demonstrated large differences in disease progression and respiratory function between genotypes. Moreover, age of onset was found to be an indicator of disease severity regardless of genotype in GNE myopathy patients. These results may help stratify patients in clinical trials and predict disease progression. [ABSTRACT FROM AUTHOR]

This research evaluated the protective role of a combined extract of Dioscorea bulbifera and Zingiber officinale (DBZO) against respiratory dysfunction caused by particulate matter (PM2.5) exposure in BALB/c mice. The bioactive compounds identified in the DBZO are catechin, astragalin, 6-gingerol, 8-gingerol, and 6-shogaol. DBZO ameliorated cell viability and reactive oxygen species (ROS) production in PM2.5-stimulated A549 and RPMI 2650 cells. In addition, it significantly alleviated respiratory dysfunction in BALB/c mice exposed to PM2.5. DBZO improved the antioxidant systems in lung tissues by modulating malondialdehyde (MDA) content, as well as levels of reduced glutathione (GSH) and superoxide dismutase (SOD). Likewise, DBZO restored mitochondrial dysfunction by improving ROS levels, mitochondrial membrane potential, and ATP production. Moreover, DBZO modulated the levels of neutrophils, eosinophils, monocytes, and lymphocytes (specifically CD4+, CD8+, and CD4+IL-4+ T cells) in blood and IgE levels in serum. DBZO was shown to regulate the c-Jun N-terminal kinase (JNK) pathway, nuclear factor kappa B (NF-κB) pathway, and transforming growth factor β (TGF-β)/suppressor of mothers against decapentaplegic (Smad) pathway. Histopathological observation indicated that DBZO mitigates the increase in alveolar septal thickness. These findings indicate that DBZO is a promising natural agent for improving respiratory health.

Objectives: The purpose of this study is to evaluate the impact of Parkinson's disease (PD) on respiratory function using spirometry. In addition, the study aims to investigate the relationship between the severity of PD and any impairments in a respiratory capacity as measured by forced vital capacity (FVC%). Methods: This case–control study (40 cases of PD vs. 40 healthy controls) was conducted from July 1, 2021, to October 31, 2022, in a tertiary care hospital of New Delhi. Clinical symptoms and severity (Movement Disorder Society Unified Parkinson's Disease Rating Scale [MDS-UPDRS] part-III score and Modified H and Y Scale) of the patients of PD were noted. A pulmonary function test (by spirometry) was performed and parameters such as forced expiratory volume in 1 s (FEV1), FVC, FEV1/FVC, and peak expiratory flow rate (PEFR) were noted. Mann–Whitney U-test (for two groups) and Chi-square test were used for the comparison of variables. Spearman rank correlation coefficient was used for the correlation of FVC (% predicted) with MDS-UPDRS part-III score and Modified H and Y stage. Results: Compared to controls, cases had significantly lower FVC% (70.5 vs. 88, P < 0.01), significantly lower FEV1% (68 vs. 83.5, P < 0.01), comparable FEV1/FVC (% predicted) (97 vs. 96, P = 0.805) and significantly lower PEFR (% predicted) (80.5 vs. 92, P < 0.01). The pattern of lung involvement was restrictive, normal, and obstructive in 72.50%, 20%, and 7.50% of cases, respectively. FVC (% predicted) showed a significant negative correlation with MDS-UPDRS part-III score (r = −0.895, P < 0.01) and with Modified H and Y Scale (r = −0.792, P < 0.01). Conclusion: Patients with PD had significantly more deranged respiratory dysfunction and there was significantly higher respiratory dysfunction with increasing severity of PD. A proper screening of lung functions may allow an early detection of respiratory dysfunction, thereby helping to initiate an early pulmonary rehabilitation to prevent respiratory complications.

The mitochondrial oxidative phosphorylation process generates most of the cellular energy and free radicals in mammalian tissues. Both factors play a critical role in numerous human diseases that could be affected by reversible phosphorylation events that regulate the function and activity of the oxidative phosphorylation complexes. In this study, we analyzed liver mitochondria of Cohen diabetes-sensitive (CDs) and Cohen diabetes-resistant (CDr) rats, using blue native gel electrophoresis (BN-PAGE) in combination with mitochondrial activity measurements and a site-specific tyrosine phosphorylation implicated in inflammation, a known driver of diabetes pathology. We uncovered the presence of a specific inhibitory phosphorylation on tyrosine 304 of catalytic subunit I of dimeric cytochrome c oxidase (CcO, complex IV). Driven by a high sucrose diet in both CDr and CDs rats, Y304 phosphorylation, which occurs close to the catalytic oxygen binding site, correlates with a decrease in CcO activity and respiratory dysfunction in rat liver tissue under hyperglycemic conditions. We propose that this phosphorylation, specifically seen in dimeric CcO and induced by high sucrose diet-mediated inflammatory signaling, triggers enzymatic activity decline of complex IV dimers and the assembly of supercomplexes in liver tissue as a molecular mechanism underlying a (pre-)diabetic phenotype. [ABSTRACT FROM AUTHOR]

Study design: Retrospective Cohort Study Objective: The purpose of this study was to investigate the prognosis of respiratory function in elderly patients with cervical spinal cord injury (SCI) and to identify predictive factors. Methods: We included 1353 cases of elderly cervical SCI patients collected from 78 institutions in Japan. Patients who required early tracheostomy and ventilator management and those who developed respiratory complications were defined as the respiratory disability group. Patients' background characteristics, injury mechanism, injury form, neurological disability, complications, and treatment methods were compared between the disability and non-disability groups. Multiple logistic regression analysis was used to examine the independent factors. Patients who required respiratory management for 6 months or longer after injury and those who died of respiratory complications were classified into the severe disability group and were compared with minor cases who were weaned off the respirator. Results: A total of 104 patients (7.8%) had impaired respiratory function. Comparisons between the disabled and non-disabled groups and between the severe and mild injury groups yielded distinct trends. In multiple logistic regression analysis, age, blood glucose level, presence of ossification of posterior longitudinal ligament (OPLL), anterior vertebral hematoma, and critical paralysis were selected as independent risk factors. Conclusion: Age, OPLL, severe paralysis, anterior vertebral hematoma, hypoalbuminemia, and blood glucose level at the time of injury were independent factors for respiratory failure. Hyperglycemia may have a negative effect on respiratory function in this condition. [ABSTRACT FROM AUTHOR]

Introduction: Aspiration pneumonia is one of the most frequent and fatal life-threatening complications among individuals with acute traumatic cervical spinal cord injury (CSCI). However, the mechanism of dysphagia among individuals with CSCI is not well understood. Morbidity and mortality associated with CSCI may result from the interplay between respiratory dysfunction and dysphagia. This study aimed to elucidate the effect of respiratory dysfunction on the swallowing function of individuals with acute traumatic CSCI. Methods: A prospective cohort study was conducted involving 54 individuals with acute traumatic CSCI who were admitted within 2 weeks following injury. Dysphagia was evaluated using the Dysphagia Severity Scale (DSS) and the Functional Oral Intake Scale (FOIS). Respiratory function was evaluated by measuring the cough peak flow (CPF), forced expiratory volume in 1 s (FEV1.0), FEV1.0/forced vital capacity (FEV1.0%), and percent vital capacity (%VC). We recorded these parameters at weeks 2, 4, 8, and 12 following injury and analyzed pertinent changes over time and significant correlations. Results: Among 54 individuals (46 men and 8 women) recruited in this study, 48 (88.9%) had restrictive ventilatory impairment and 17 (31.5%) had severe dysphagia (DSS level 1−4) 2 weeks following injury. However, respiratory function and swallowing function significantly improved thereafter. CPF, FEV1.0, and %VC were significantly correlated with the severity of dysphagia during each period. Conclusions: Restrictive ventilatory impairment, poor cough force, and dysphagia are closely related, and the evaluation of respiratory function plays an important role in evaluating dysphagia.

Purpose: To investigate the impact of early post-injury respiratory dysfunction for neurological and ambulatory ability recovery in patients with cervical spinal cord injury (SCI) and/or fractures. Methods: We included 1,353 elderly patients with SCI and/or fractures from 78 institutions in Japan. Patients who required early tracheostomy and ventilator management and those who developed respiratory complications were included in the respiratory dysfunction group, which was further classified into mild and severe respiratory groups based on respiratory weaning management. Patient characteristics, laboratory data, neurological impairment scale scores, complications at injury, and surgical treatment were evaluated. We performed a propensity score-matched analysis to compare neurological outcomes and mobility between groups. Results: Overall, 104 patients (7.8%) had impaired respiratory function. In propensity score-matched analysis, the respiratory dysfunction group had a lower home discharge and ambulation rates (p = 0.018, p = 0.001, respectively), and higher rate of severe paralysis (p < 0.001) at discharge. At the final follow-up, the respiratory dysfunction group had a lower ambulation rate (p = 0.004) and higher rate of severe paralysis (p < 0.001). Twenty-six patients with severe disability required respiratory management for up to 6 months post-injury and died of respiratory complications. The mild and severe respiratory dysfunction groups had a high percentage of severe paraplegic cases with low ambulatory ability; there was no significant difference between them. The severe respiratory dysfunction group tended to have a poorer prognosis. Conclusion: Respiratory dysfunction in elderly patients with SCI and/or cervical fracture in the early post-injury period reflects the severity of the condition and may be a useful prognostic predictor. [ABSTRACT FROM AUTHOR]

Use of sugammadex is associated with fewer postoperative pulmonary complications (PPCs). This study investigated the relationship between sugammadex and PPCs in specific patients with respiratory dysfunction. We reviewed the electronic medical and anesthesia records of patients with respiratory dysfunction who underwent laparoscopic gastric or intestinal surgery at a single center between May 1, 2018 and December 31, 2019. The patients were divided into the sugammadex group and the nonsugammadex group, based on whether they received sugammadex or neostigmine. Binary logistic regression analyses were used to characterize the differences in incidence of PPC. A total of 112 patients were included, of which 46 patients (41.1%) received sugammadex. In the logistic regression analysis, the incidences of PPC were fewer in the sugammadex group. Postoperative fever (odds ratio [OR] 0.330; 95% confidence interval [CI] 0.137-0.793, P = 0.0213), postoperative intensive care unit admission (OR 0.204; 95% CI 0.065-0.644, P = 0.007), cough (OR 0.143; 95% CI 0.061- 0.333, P < 0.001), pleural effusion (all) (OR: 0.280; 95% CI 0.104- 0.759, P = 0.012), pleural effusion (massive) (OR: 0.142; 95% CI 0.031- 0.653, P = 0.012), and difficulty in breathing (OR: 0.111; 95% CI 0.014-0.849, P = 0.039) showed significant differences between the two groups. Sugammadex is associated with a reduction in PPC in patients with respiratory dysfunction. [ABSTRACT FROM AUTHOR]

• Suitability of Respicheck and ESS for IMT monitoring not met. • No significant correlation between PROMs and lung function in subgroup analysis. • Significant improvements in respiratory function assessments after IMT. • High incidence of hypoventilation symptoms in DM1. Myotonic dystrophy type 1 (DM1) is an autosomal dominant trinucleotide disorder that often leads to respiratory dysfunction resulting in hypoventilation symptoms, reduced quality of life and causing premature death if untreated. To early identify symptoms of hypoventilation, the Respicheck questionnaire was developed as a screening tool. Symptomatic therapies like inspiratory muscle training (IMT) are recommended to strengthen respiratory muscles and reduce or even prevent hypoventilation symptoms. Our study aimed to evaluate the Respicheck questionnaire's suitablility to monitor the efficacy of IMT. Patients with genetically confirmed DM1 were randomly assigned to either IMT – endurance or strength training, or control group. At baseline, end of study and four interim visits, pulmonary function tests, Respicheck questionnaire and Epworth sleepiness scale were assessed. While patients in training groups achieved a substantial improvement after nine months of regular IMT in pulmonary function tests, the Respicheck score did not improve likewise. Similarly, the ESS score did not change significantly in both training and control groups. Consequently, we conclude that either improvement of respiratory function is not necessarily associated with clinical improvement, or respiratory muscle weakness was not the only reason for hypoventilation syndrome, or both questionnaires are not sensitive enough to detect slight clinical changes. [ABSTRACT FROM AUTHOR]

Respiration is a crucial steady-state function of human life. Central nervous system injury can damage the central respiratory pattern generator (CRPG) or interrupt its outflow, leading to central respiratory paralysis and dysfunction, which can endanger the patient's life. At present, there is no effective means to reverse this process. Commonly used non-invasive neuromodulation techniques include repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and so forth, which have been widely applied in nervous system diseases and their various secondary symptoms, but rarely in respiratory function. Clinical and animal studies have confirmed that TMS is also suitable for investigating the excitability and plasticity of ascending corticospinal respiratory pathways. In addition, although rTMS and tDCS differ in their respective mechanisms, both can regulate respiratory networks in healthy individuals and in diseased states. In this review, we provide an overview of the physiology of respiration, the use of TMS to assess the excitability of corticophrenic pathways in healthy individuals and in central respiratory disorders, followed by an overview of the animal and clinical studies of rTMS, tDCS and so forth in regulating respiratory circuits and the possible mechanisms behind them. It was found that the supplementary motor area (SMA) and the phrenic motor neuron (PMN) may be key regulatory areas. Finally, the challenges and future research directions of neuroregulation in respiratory function are proposed. Through understanding how neuromodulation affects the respiratory neural circuit non-invasively, we can further explore the therapeutic potential of this neuromodulation strategy, so as to promote the recovery of respiratory function after central nervous system diseases or injury. [ABSTRACT FROM AUTHOR]

Pompe disease is an autosomal recessive glycogen storage disease caused by mutations in the gene that encodes acid alpha-glucosidase (GAA)—an enzyme responsible for hydrolyzing lysosomal glycogen. GAA deficiency results in systemic lysosomal glycogen accumulation and cellular disruption. Glycogen accumulation in skeletal muscles, motor neurons, and airway smooth muscle cells is known to contribute to respiratory insufficiency in Pompe disease. However, the impact of GAA deficiency on the distal alveolar type 1 and type 2 cells (AT1 and AT2) has not been evaluated. AT1 cells rely on lysosomes for cellular homeostasis so that they can maintain a thin barrier for gas exchange, whereas AT2 cells depend on lysosome-like structures (lamellar bodies) for surfactant production. Using a mouse model of Pompe disease, the Gaa-1- mouse, we investigated the consequences of GAA deficiency on AT1 and AT2 cells using histology, pulmonary function and mechanics, and transcriptional analysis. Histological analysis revealed increased accumulation of lysosomal-associated membrane protein 1 (LAMP1) in the Gaa-1- mice lungs. Furthermore, ultrastructural examination showed extensive intracytoplasmic vacuoles enlargement and lamellar body engorgement. Respiratory dysfunction was confirmed using whole body plethysmography and forced oscillometry. Finally, transcriptomic analysis demonstrated dysregulation of surfactant proteins in AT2 cells, specifically reduced levels of surfactant protein D in the Gaa-1- mice. We conclude that GAA enzyme deficiency leads to glycogen accumulation in the distal airway cells that disrupts surfactant homeostasis and contributes to respiratory impairments in Pompe disease. NEW & NOTEWORTHY This research highlights the impact of Pompe disease on distal airway cells. Prior to this work, respiratory insufficiency in Pompe disease was classically attributed to pathology in respiratory muscles and motor neurons. Using the Pompe mouse model, we note significant pathology in alveolar type 1 and 2 cells with reductions in surfactant protein D and disrupted surfactant homeostasis. These novel findings highlight the potential contributions of alveolar pathology to respiratory insufficiency in Pompe disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The Nijmegen Questionnaire (NQ) enables the assessment and identification of symptoms related to respiratory dysfunction and hyperventilation syndrome. The aim was to investigate the validity of the Turkish version of the NQ in asthmatics. MATERIAL AND METHODS: Fifty-four individuals with asthma were included. Spirometry was performed. Dyspnea was assessed using the modified Borg and modified Medical Research Council scales. Breath-holding time was recorded. End-tidal carbon dioxide was measured using a portable capnograph. Oxygen saturation and heart rate were recorded. Asthma Control Test was used to evaluate the asthma control level. Quality of life was assessed using the Asthma Quality of Life Questionnaire and Nottingham Health Profile. Beck Depression Inventory was used to determine depression. RESULTS: Bartlett's test of sphericity (360.749, df 105, P < .001) and Kaiser-Meyer-Olkin criterion (0.752) for 15-item NQ supported a single-factor model with 36.38% of explained variability through principal component analysis and explanatory factor analysis. For 15-item NQ with this single-factor model, Cronbach's alpha was 0.872, and the test-retest reliability was 0.628. There was a significant negative correlation between NQ and Asthma Control Test (r = -0.448), and Asthma Quality of Life Questionnaire (r = -0.743) and a significant positive association with Beck Depression Inventory (r = 0.477), Nottingham Health Profile--energy (r = 0.370), Nottingham Health Profile--pain (r = 0.313), Nottingham Health Profile--sleep (r = 0.294), and Nottingham Health Profile--physical activity scores (r = 0.406) (P < .05). CONCLUSIONS: The 15-item Turkish version of the NQ is valid and reliable in asthmatics. Individuals with uncontrolled asthma have higher NQ scores than those with well-controlled asthma. NQ is associated with asthma control level, asthma-related quality of life, health profile, and depression. [ABSTRACT FROM AUTHOR]

Abstract Dementia with Lewy bodies (DLB) is the second most common cause of dementia after Alzheimer's disease. The disease is characterized by many Lewy bodies appearing in the patient's cerebrum. DLB frequently presents with a variety of autonomic symptoms from the early or prodromal stages of the disease, and these are listed as supportive features in the diagnostic criteria. As several useful assessment methods for evaluating autonomic function in DLB have been reported, this review will focus on cardiovascular and respiratory dysfunction and its assessments. Cardiovascular disorders, such as orthostatic hypotension and abnormal heart rate variability, have been reported in DLB patients. Decreased myocardial uptake by metaiodobenzylguanidine myocardial scintigraphy has been added as an indicative biomarker for DLB in the 2017 revision of the diagnostic criteria. We have reported reduced ventilatory response to hypercapnia, abnormal respiratory rhythm, and high frequency of sleep‐disordered breathing as abnormalities of the respiratory regulatory system associated with DLB. Since autonomic dysfunction is highly prevalent in DLB from the early or prodromal phase of the disease and is associated with reduced activities of daily living and quality of life, the evaluation of autonomic dysfunction is also useful in the differential diagnosis of DLB from Alzheimer's disease. There are fewer studies on the respiratory regulatory system than on the cardiovascular system, thus further research is needed to explore its role in DLB.

Background: The main aim of this umbrella review was to assess the respiratory function in patients with chronic pain (CP), including patients with chronic neck pain (CNP), chronic low back pain (CLBP), and fibromyalgia syndrome (FMS). Methods: We searched in PubMed, PEDro, EMBASE, CINAHL, and Google Scholar (4 February 2023). The outcome measures were respiratory muscle strength (MIP/MEP) and pulmonary function (VC, MVV, FVC, FEV1, FEV1/FVC ratio, FEV25–75, and PEF). This review was previously registered in the international prospective register of systematic reviews, PROSPERO (CRD42023396722). The methodological quality was analyzed using AMSTAR and ROBIS scales, and the strength of the evidence was established according to the guidelines advisory committee grading criteria. To compare the outcomes reported by the studies, we calculated the standardized mean differences and the corresponding 95% confidence interval for the continuous variables. Results: Four systematic reviews with and without meta-analysis were included, from which a total of 15 primary studies were extracted. Five meta-analyses were carried out, using analyses by subgroup according to the type of CP. The meta-analyzing variables were MIP, MEP, MVV, FEV1, and FVC. Conclusions: Overall, patients with CP have decreased respiratory muscle strength with a moderate quality of evidence. Regarding the pulmonary function, patients with CNP showed a diminished VC, PEF, MVV, FEV1, and FVC, while FEV25–75 and the FEV1/FVC ratio were conserved with a limited to moderate quality of evidence. Finally, patients with FMS and CLBP only showed a decrease in MVV with a limited quality of evidence. [ABSTRACT FROM AUTHOR]

The mitochondrial oxidative phosphorylation process generates most of the cellular energy and free radicals in mammalian tissues. Both factors play a critical role in numerous human diseases that could be affected by reversible phosphorylation events that regulate the function and activity of the oxidative phosphorylation complexes. In this study, we analyzed liver mitochondria of Cohen diabetes-sensitive (CDs) and Cohen diabetes-resistant (CDr) rats, using blue native gel electrophoresis (BN-PAGE) in combination with mitochondrial activity measurements and a site-specific tyrosine phosphorylation implicated in inflammation, a known driver of diabetes pathology. We uncovered the presence of a specific inhibitory phosphorylation on tyrosine 304 of catalytic subunit I of dimeric cytochrome c oxidase (CcO, complex IV). Driven by a high sucrose diet in both CDr and CDs rats, Y304 phosphorylation, which occurs close to the catalytic oxygen binding site, correlates with a decrease in CcO activity and respiratory dysfunction in rat liver tissue under hyperglycemic conditions. We propose that this phosphorylation, specifically seen in dimeric CcO and induced by high sucrose diet-mediated inflammatory signaling, triggers enzymatic activity decline of complex IV dimers and the assembly of supercomplexes in liver tissue as a molecular mechanism underlying a (pre-)diabetic phenotype.

Introduction: We aimed to clarify the differences in static and dynamic diaphragm parameters between the expiratory and inspiratory phases in amyotrophic lateral sclerosis (ALS).Methods: Twenty patients with early-stage ALS and 16 healthy controls were enrolled in the study. We measured the amplitudes of compound muscle action potential (phCMAP) by electrical stimulation of the phrenic nerve and the zone of apposition wall thickness of the diaphragm (DT) using ultrasonography. We analyzed the differences in phCMAP (∆phCMAP) and DT (∆DT) between the end-inspiratory and end-expiratory phases and their correlation with forced vital capacity (FVC).Results: The ΔphCMAP (mean 129.7 ± SD 204.7 µV) and ∆DT (0.80 ± 0.88 cm) in patients were significantly smaller than those in controls (348.6 ± 247.7 µV, p = 0.0003 and 1.89 ± 1.10 cm, p = 0.0002, respectively). Although ∆DT was significantly correlated with FVC, we found no correlation between ∆phCMAP and FVC. The phCMAP was paradoxically smaller during inspiration than during expiration in 35% of patients but in none of the controls.Conclusion: Dynamic parameters of the diaphragm were abnormal in early-stage ALS. The paradoxical reduction in phCMAP during inspiration may reflect early respiratory dysfunction. Assessment of dynamic abnormalities of the diaphragm may provide helpful information for respiratory management in patients with ALS. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting around 10 million people worldwide. It is primarily associated with the loss of dopaminergic neurons in the substantia nigra pars compacta, though the exact mechanism is unclear. PD is characterized by resting tremor, muscular rigidity, bradykinesia, and postural instability. These motor symptoms, resulting from impaired muscle function, can lead to dysphagia and respiratory dysfunction. It is suggested that the muscular rigidity and bradykinesia in PD may impair repetitive motor actions, negatively impacting respiration. While less studied, PD-related respiratory dysfunction could stem from obstructive, restrictive, or CNS disturbances. This case report discusses a 69-year-old male with PD and dementia presented at an assisted living facility in Palmar Sur, Costa Rica, with difficulty exhaling after deep inhalation. Physical examination revealed typical PD symptoms (resting tremor, muscular rigidity, bradykinesia, postural instability) along with hypotension, bradycardia, and bradypnea. Respiratory assessment showed he could inhale but had difficulty exhaling, suggesting a myotonic-like pathology. The cogwheel-like rigidity during exhalation is unique and points to a myotonic-like respiratory dysfunction related to his PD, a presentation not commonly observed in PD patients. Research suggests respiratory impairments in PD may result from issues with central ventilatory control, restrictive lung disease (reduced lung capacity), or obstructive lung disease (blocked airflow). Restrictive mechanisms might stem from thoracic rigidity and posture changes, while obstructive factors could be exacerbated by the patient's smoking history. Respiratory muscle fatigue may arise from the demands of repetitive ventilation. Additionally, degeneration in the brain's respiratory center, possibly linked to α-synuclein deposits, could affect respiratory regulation. Osteopathic Manipulation Treatment (OMT) may help alleviate these symptoms by improving thoracic flexibility and respiratory function. Overall, this case highlights the varied presentations of PD, focusing on the lens respiratory dysfunction, possibly due to respiratory muscle rigidity or central nervous system involvement. Recognizing these symptoms is crucial for early intervention and preventing complications like aspiration pneumonia, a major cause of morbidity and mortality in PD. Further research is needed to better understand the relationship between PD and respiratory dysfunction., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Rundquist et al.)

Background: Respiratory impairment is a problem seen in people with multiple sclerosis (pwMS) from the early stages of the disease but not frequently recognized by clinicians until the later stages. It is seen in different ways, such as respiratory muscle weakness, change in pulmonary volumes, and decrease in cough efficiency. This situation has consequences affecting individuals’ physical fitness, participation in daily life, and quality of life. Summary: This review explains possible respiratory impairment mechanisms, related problems, assessment, and rehabilitation approaches in pwMS. Key Messages: It is recommended a comprehensive assessment of respiratory functions in pwMS regardless of the disease severity and stage. In addition, pulmonary rehabilitation and other exercises can have positive effects on the respiratory functions of pwMS. In future studies, specific training parameters should be determined for pwMS to achieve optimal benefits. There is also a need for studies that apply respiratory muscle training in pwMS who have a high disease severity and limited participation in the activities of daily living.

Phrenic nerve dysfunction has been associated with cervical neuroforaminal stenosis in limited case reports and case-controlled studies. It is unclear if magnetic resonance imaging of the cervical spine should be included in the workup of patients with pulmonary dysfunction. A systematic review of the current literature was conducted on the topic to provide an outline of the body of knowledge and some guidance for neurosurgeons that receive these patient referrals. A systematic literature review was conducted through the PubMed database to identify articles related to phrenic nerve dysfunction secondary to cervical stenosis. A total of 12 case reports were found. The median subject age was 64 years, 11 were male. Presenting symptoms included shortness of breath (n = 9), radiculopathy (n = 7), myelopathy (n = 5), reduced pulmonary function (n = 6), weakness (n = 4), and neck pain (n = 5). Ten of these patients underwent surgical intervention, all having improvements in their pulmonary and neurological symptoms at follow-up ranging from 10 days to 2 years. Cervical stenosis, resulting in neuroforaminal stenosis, may be related to phrenic nerve dysfunction in select patients with idiopathic diaphragmatic paralysis or pulmonary dysfunction. Surgical decompression improves pulmonary and neurological symptoms. [ABSTRACT FROM AUTHOR]

Until now, non-specific chronic neck pain has mainly been considered as a musculoskeletal system dysfunction, with associated psychological involvement due to its prolonged or recurrent nature. However, patients with non-specific chronic neck pain frequently additionally exhibit respiratory dysfunction. Emerging evidence suggests that addressing the respiratory dysfunction in these patients will provide additional therapeutic benefits in musculoskeletal and respiratory-related outcomes for several reasons (biomechanical, biochemical, and psychological). Motor control dysfunction of the muscles surrounding the spine (diaphragm included) negatively affects the mechanics and biochemistry of breathing (pH-homeostasis). An impaired and ineffective breathing pattern has been recognized as the primary source of many unexplained symptoms (anxiety, depression, confusion, chest pain, hypocapnia, and breathlessness) in patients with non-specific chronic neck pain. The proposed protocol's purpose is dual: to assess the relative effectiveness of manual therapy in the cervical spine and the diaphragm, in combination with breathing reeducation exercises, along with cervical spine manual therapy or usual physical therapy care on the underlying dysfunctions in patients with non-specific chronic neck pain via a randomized controlled clinical trial, and to validate part of the outcome measures. Several musculoskeletal and respiratory dysfunction outcomes will be employed to delimit the initial extent and level of dysfunction and its resolution with the treatments under study. [ABSTRACT FROM AUTHOR]

EEF1A2 is a gene whose protein product, eukaryotic translation elongation factor 1 alpha 2 (eEF1A2), plays an important role in neurodevelopment. Reports of individuals with pathogenic variants in EEF1A2 are rare, with less than 40 individuals reported world‐wide, however a common feature is the association of the variant with developmental and epileptic encephalopathy. Thus far, there have been limited reports of other organ systems or body functions affected by variants in this gene. Here, we present a case of a child with EEF1A2‐related disorder who presented at 3 months of age with hypotonia, microcephaly, failure to thrive, and respiratory insufficiency with central apneas requiring respiratory support. Our case highlights the notion that the respiratory system may be highly implicated in EEF1A2‐related disorder, allowing for better phenotypic characterization of the disorder. [ABSTRACT FROM AUTHOR]

Background: To assess respiratory function in cervical chronic compressive myelopathy (CCM) patients in pre-operative period, post-operative period and to compare pre-operative status with post-operative status. Aims and Objectives: 1. To assess respiratory function in cervical CCM patients in pre-operative period. 2. To assess respiratory function in cervical CCM patients in post-operative period, following relief of compression. 3. To compare, pre-operative status with post-operative status. Materials and Methods: A prospective study was done in 50 patients with cervical CCM due to either cervical disc disease or ossified posterior longitudinal ligament (OPLL) who were operated. None of the patients included in the study had any clinical signs & symptoms of respiratory dysfunction. Spirometry was performed in pre-operative and postoperative period after 3 months and results were analyzed. Forced vital capacity (FVC), forced expiratory volume in first second (FEV1), ratio of mean FEV1 to FVC (FEVI: FVC%) and peak expiratory flow rate (PEFR) were calculated. Results: Majority of the patients were in their fourth decade of life with male predominance. Thirty-six patients (72%) presented with prolapsed intervertebral disc and 14 patients (28%) had ossified posterior longitudinal ligament (OPLL). Patients were operated depending upon the pathology. The present study showed that there was significant reduction in preoperative FVC, FEV1, PEFR values as compared with predicted values and they showed significant improvement in post-operative period after surgical relief of compression. Conclusion: Significant yet occult respiratory dysfunction in form of impairment of various lung capacities exists in patients with cervical CCM. An objective evaluation of this occult respiratory dysfunction is essential to prognosticate, prevent respiratory complications and to improve post-operative respiratory rehabilitation. Institution of incentive spirometry as a routine in all cervical CCM cases will be of benefit in preventing respiratory complications.

The heart and lung are in continuous reciprocal interaction that creates a functional and anatomical reserve referred to as cardiopulmonary coupling (CPC). Disruption of CPC can occur due to various cardiac or pulmonary pathologies but also can occur in patients with myopathies. Nemaline myopathy (NM) is a skeletal muscle heterogeneous disorder due to contractile proteins' gene mutations that impact lung and cardiac mechanics and thus is expected to adversely affect CPC in a complex manner. We present a case of NM and we review the literature on cardiac and pulmonary effects of myopathy-related disruption of CPC.

Failure to recover from repeated hypercapnia and hypoxemia (HH) challenges caused by severe GCS and postictal apneas may contribute to sudden unexpected death in epilepsy (SUDEP). Our previous studies found orexinergic dysfunction contributes to respiratory abnormalities in a preclinical model of SUDEP, Kcna1 −/− mice. Here, we developed two gas challenges consisting of repeated HH exposures and used whole body plethysmography to determine whether Kcna1 −/− mice have detrimental ventilatory responses. Kcna1−/− mice exhibited an elevated ventilatory response to a mild repeated hypercapnia-hypoxia (HH) challenge compared to WT. Moreover, 71% of Kcna1−/− mice failed to survive a severe repeated HH challenge, whereas all WT mice recovered. We next determined whether orexin was involved in these differences. Pretreating Kcna1−/− mice with a dual orexin receptor antagonist rescued the ventilatory response during the mild challenge and all subjects survived the severe challenge. In ex vivo extracellular recordings in the lateral hypothalamus of coronal brain slices, we found reducing pH either inhibits or stimulates putative orexin neurons similar to other chemosensitive neurons; however, a significantly greater percentage of putative orexin neurons from Kcna1−/−mice were stimulated and the magnitude of stimulation was increased resulting in augmentation of the calculated chemosensitivity index relative to WT. Collectively, our data suggest that increased chemosensitive activity of orexin neurons may be pathologic in the Kcna1−/− mouse model of SUDEP, and contribute to elevated ventilatory responses. Our preclinical data suggest that those at high risk for SUDEP may be more sensitive to HH challenges, whether induced by seizures or other means; and the depth and length of the HH exposure could dictate the probability of survival. • Kcna1 −/− mice have altered ventilatory responses and succumb to severe HH tests. • Orexinergic blockade improves ventilation and survival in Kcna1 −/− mice during HH. • Kcna1 −/− putative orexin neurons have greater chemosensitive activity. [ABSTRACT FROM AUTHOR]

Patients with nonspecific chronic neck pain (NSCNP) exhibit respiratory dysfunction. This systematic review aimed to analyze randomized controlled trials (RCTs) investigating the effect of spinal and/or diaphragmatic and/or specific stabilization exercise manual therapy and/or respiratory exercises on musculoskeletal and respiratory diagnostic outcomes in patients with NSCNP. A systematic search and selection of RCTs was performed in three scientific databases (Pubmed, Scopus, and Physiotherapy Evidence Database (PEDro)) and one search engine (Google Scholar) from inception to April 2022. Relevant studies published in the English language were extracted, evaluated, and independently rated for methodological quality (PEDro scale). The quality of the evidence was assessed with the GRADE approach. Out of 1089 studies collected in total, 1073 were excluded (i.e., did not meet the inclusion criteria or were duplicates). Sixteen RCTs were finally included, rated on 5.62/10 (PEDro score) on average for methodological quality. Overall, there was sparse evidence that spinal and/or diaphragmatic manual therapy and/or trunk stabilization exercises and/or respiratory exercises significantly improved pain, disability, and respiratory outcomes in patients with NSCNP immediately post-treatment. However, the clinical heterogeneity between studies was significant, and the level of certainty of the evidence was low to very low. More, high-quality RCTs are required, contributing to the holistic diagnostic monitoring and management of patients with NSCNP. [ABSTRACT FROM AUTHOR]

Early Parkinson's disease (PD) may cause respiratory dysfunction; however the findings vary among studies. The aim of the preliminary prospective observational study was to explore the deterioration of pulmonary function at various stages in patients with early PD. A total of 237 patients with PD were screened. Fifty-six patients were included (modified Hoehn and Yahr stage ≤ 2.5). In addition, 56 age-matched healthy controls were also included in the study. Significant differences between the PD and control groups were found in all the investigated lung-function parameters. The maximal voluntary ventilation (MVV) percent predicted was the only parameter that distinguished PD stages (101.1 ± 14.9% vs. 82.8 ± 19.2% vs. 71.4 ± 12.9%, Hoehn and Yahr stages 1.5 vs. 2 vs. 2.5, respectively; p < 0.005). MVV could be the most sensitive parameter for distinguishing the severity of early-stage PD. [ABSTRACT FROM AUTHOR]

ObjectiveThe pathophysiology of sudden unexpected death in epilepsy (SUDEP) remains undetermined. Seizures are accompanied by respiratory dysfunction (RD). Postictal generalized electroencephalography (EEG) suppression (PGES) may follow generalized tonic-clonic seizures (GTCS). Following GTCS patients have impaired arousal and may be motionless. Patients with SUDEP are usually prone. Postictal immobility (PI) may contribute to SUDEP by not permitting repositioning of the head to allow unimpeded ventilation. To determine whether RD and/or ictal characteristics are associated with PI, we analyzed patients with GTCS in the epilepsy monitoring unit.MethodWe investigated for associations between PI duration and PGES, ictal/postictal oxygen saturation (SpO2 ), end-tidal CO2 (ETCO2 ), seizure localization, duration, and tonic and total convulsive phase duration. We investigated for linkage between PGES and these measures.ResultsSeventy patients with 181 GTCS and available SpO2 and/or ETCO2 data were studied. Simple linear regression analysis by seizures showed that PI duration was associated with peak periictal ETCO2 (p = 0.03), duration of oxygen desaturation (p = 0.005) and with SpO2 nadir (p = 0.02). PI duration was not associated with tonic, convulsive phase or total seizure duration. Analysis by patients also showed significant association of PI with RD. Duration of PI was longer following seizures with PGES (p < 0.001). PGES was not associated with the tonic, convulsive phase or total seizure duration. SpO2 nadir was lower in seizures with PGES (p = 0.046), ETCO2 peak change (p = 0.003) was higher, and duration of ETCO2 elevation (p = 0.03) was longer. Multivariable regression analysis showed that PGES and severe RD were associated with PI duration.SignificanceThe duration of PI and presence of PGES are associated with periictal RD. The duration of PI is also associated with the presence of PGES. Seizure duration or duration of the convulsive phase is not associated with PI or PGES. Interventions aimed at reversing impaired arousal and PI may reduce SUDEP risk.

Background/aim: To reveal the potential efficiency of high-flow oxygen therapy in acute pancreatitis complicated with acute respiratory dysfunction compared with conventional oxygen therapy. Materials and methods: We retrospectively analyzed 69 patients treated with high-flow oxygen or conventional oxygen therapy, then compared the difference of prime and second outcomes between the two groups. Results: The high-flow oxygen group had lower intubation rate (25.6% vs. 56.7%, p = 0.013) and longer median time to intubation (64.25 h vs. 7.75 h, p < 0.001) compared with the conventional oxygen group. High-flow oxygen had a stronger effect on improving dyspnea (87.2% vs. 56.7%, p = 0.006) and regression of respiratory failure (66.7% vs. 26.7%, p = 0.001). In the univariate and multivariate analyses, high-flow oxygen and APACHE II score were independent predict factors to respiratory failure regression (OR = 20.381, p = 0.038; OR = 36.827, p = 0.026). Patients treated with high-flow oxygen had shorter intensive care unit stay length (19.5 ± 13.4 vs. 7.8 ± 4.7, p = 0.009) and early mortality tended to be significantly lower (17.9% vs. 40.0%, p = 0.058). Conclusion: High-flow oxygen is a more effective method for acute pancreatitis complicated with acute respiratory dysfunction than conventional oxygen therapy. [ABSTRACT FROM AUTHOR]

A 15‐year‐old male presented with headache, high fever and respiratory distress. Chest computed tomography showed bilateral pneumonia, and antimicrobial therapy was initiated. However, his respiratory condition deteriorated, and he developed respiratory failure requiring intubation. A multiplex polymerase chain reaction (PCR) test and 16S ribosomal RNA gene analysis were done from his intratracheal secretions to determine the causative pathogens, and Mycoplasma pneumoniae was detected. He was treated with appropriate antimicrobial therapy, systemic corticosteroid therapy and extracorporeal membrane oxygenation. He also presented with pulmonary thromboembolism and was treated with anticoagulants, to which he responded well. This patient demonstrates the similarities between severe M. pneumoniae pneumonia with bilateral pneumonitis and thrombosis, and severe coronavirus disease 2019. Therefore, it is important to identify cases of bilateral pneumonia with severe respiratory dysfunction using multiplex PCR tests to provide appropriate medical management and therapeutic interventions. [ABSTRACT FROM AUTHOR]

There is a group of diseases such as low back pain, osteoporosis, fibromyalgia and obesity for which pulmonary rehabilitation can be applied. Although these diseases do not directly impact the lungs, respiratory dysfunction occurs through various mechanisms during the disease process and complicates the underlying primary disease. Respiratory dysfunction and spirometric abnormalities have been observed from the early stages of these diseases, even without obvious signs and symptoms. These patients should be carefully evaluated for pulmonary problems as a sedentary lifestyle may hide the presence of respiratory symptoms. Once pulmonary problems have been detected, pulmonary rehabilitation should be added to the routine treatment of the primary disease. [ABSTRACT FROM AUTHOR]

Background: Breathing abnormalities are common in Rett syndrome (RTT), a pervasive neurodevelopmental disorder almost exclusively affecting females. RTT is linked to mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. Our aim was to assess the clinical relevance of apneas during sleep-wakefulness cycle in a population with RTT and the possible impact of apneas on circulating oxidative stress markers. Methods: Female patients with a clinical diagnosis of typical RTT (n = 66), MECP2 gene mutation, and apneas were enrolled (mean age: 12.5 years). Baseline clinical severity, arterial blood gas analysis, and red blood cell count were assessed. Breathing was monitored during the wakefulness and sleep states (average recording time: 13 ± 0.5 h) with a portable polygraphic screening device. According to prevalence of breath holdings, the population was categorized into the wakefulness apnea (WA) and sleep apnea (SA) groups, and apnea-hypopnea index (AHI) was calculated. The impact of respiratory events on oxidative stress was assessed by plasma and intra-erythrocyte non-protein-bound iron (P-NPBI and IE-NPBI, respectively), and plasma F2-isoprostane (F2-IsoP) assays. Results: Significant prevalence of obstructive apneas with values of AHI > 15 was present in 69.7% of the population with RTT. The group with SA showed significantly increased AHI values > 15 (p = 0.0032), total breath holding episodes (p = 0.007), and average SpO2 (p = 0.0001) as well as lower nadir SpO2 (p = 0.0004) compared with the patients with WAs. The subgroups of patients with WA and SA showed no significant differences in arterial blood gas analysis variables (p > 0.089). Decreased mean cell hemoglobin (MCH) (p = 0.038) was observed in the group with WAs. P-NPBI levels were significantly higher in the group with WA than in that with SAs (p = 0.0001). Stepwise multiple linear regression models showed WA being related to nadir SpO2, average SpO2, and P-NPBI (adjusted R 2 = 0.613, multiple correlation coefficient = 0.795 p < 0.0001), and P-NPBI being related to average SpO2, blood PaCO2, red blood cell mean corpuscular volume (MCV), age, and topiramate treatment (adjusted R 2 = 0.551, multiple correlation coefficient = 0.765, p < 0.0001). Conclusion: Our findings indicate that the impact of apneas in RTT is uneven according to the sleep-wakefulness cycle, and that plasma redox active iron represents a potential novel therapeutic target. [ABSTRACT FROM AUTHOR]

BackgroundBreathing abnormalities are common in Rett syndrome (RTT), a pervasive neurodevelopmental disorder almost exclusively affecting females. RTT is linked to mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. Our aim was to assess the clinical relevance of apneas during sleep-wakefulness cycle in a population with RTT and the possible impact of apneas on circulating oxidative stress markers.MethodsFemale patients with a clinical diagnosis of typical RTT (n = 66), MECP2 gene mutation, and apneas were enrolled (mean age: 12.5 years). Baseline clinical severity, arterial blood gas analysis, and red blood cell count were assessed. Breathing was monitored during the wakefulness and sleep states (average recording time: 13 ± 0.5 h) with a portable polygraphic screening device. According to prevalence of breath holdings, the population was categorized into the wakefulness apnea (WA) and sleep apnea (SA) groups, and apnea-hypopnea index (AHI) was calculated. The impact of respiratory events on oxidative stress was assessed by plasma and intra-erythrocyte non-protein-bound iron (P-NPBI and IE-NPBI, respectively), and plasma F2-isoprostane (F2-IsoP) assays.ResultsSignificant prevalence of obstructive apneas with values of AHI > 15 was present in 69.7% of the population with RTT. The group with SA showed significantly increased AHI values > 15 (p = 0.0032), total breath holding episodes (p = 0.007), and average SpO2 (p = 0.0001) as well as lower nadir SpO2 (p = 0.0004) compared with the patients with WAs. The subgroups of patients with WA and SA showed no significant differences in arterial blood gas analysis variables (p > 0.089). Decreased mean cell hemoglobin (MCH) (p = 0.038) was observed in the group with WAs. P-NPBI levels were significantly higher in the group with WA than in that with SAs (p = 0.0001). Stepwise multiple linear regression models showed WA being related to nadir SpO2, average SpO2, and P-NPBI (adjusted R2 = 0.613, multiple correlation coefficient = 0.795 p < 0.0001), and P-NPBI being related to average SpO2, blood PaCO2, red blood cell mean corpuscular volume (MCV), age, and topiramate treatment (adjusted R2 = 0.551, multiple correlation coefficient = 0.765, p < 0.0001).ConclusionOur findings indicate that the impact of apneas in RTT is uneven according to the sleep-wakefulness cycle, and that plasma redox active iron represents a potential novel therapeutic target.

Background: Dyspnea is an important non-motor symptom in Parkinson's disease (PD) that impacts quality of life. The mechanisms underlying dyspnea have been difficult to determine due to challenges separating central respiratory control abnormalities from peripheral respiratory muscle dysfunction and chest wall rigidity., Methods: A comprehensive literature review was conducted, searching the PubMed database for observational studies on respiratory dysfunction and dyspnea in PD. Inclusion criteria were studies with PD patients without other neurological disorders. Case studies were excluded. Data on study size, disease duration, control groups, and respiratory defects were extracted., Results: The search yielded 23 unique publications on pulmonary function in PD. Key findings were: 1) restrictive defects are common, with prevalence up to 85 % in some studies; 2) effects of levodopa on pulmonary function are variable across studies; 3) there is limited research on the role of central respiratory centers in dyspnea pathophysiology in PD. Proposed mechanisms include direct involvement of brainstem respiratory structures, loss of dopamine input to these regions, and astrocyte dysfunction affecting respiratory rhythm generation., Conclusion: This review outlines potential mechanisms underlying dyspnea in PD, including central respiratory dysfunction, peripheral muscle/chest wall abnormalities, impaired respiratory sensation, and medication effects. More research is needed investigating specific brainstem regions involved, chemoreceptor pathology, correlations between respiratory load and perceived dyspnea, and medication effects on pulmonary function., Competing Interests: Declaration of competing interest Suyash Jain, Shruti Patel, and Kenneth Nugent have nothing to declare related to this particular project., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We encountered a 67-year-old Japanese man with GNE myopathy and homozygous variants (c.1807G>C, p.V603L) of the GNE gene. The patient developed weakness in the left foot at 24 years old and could only move his wrist joints and hands 43 years after the onset. This genotype is the most common variant and causes severe muscle involvement; however, the distal upper extremities are preserved until the end-stage of the disease. Although severe heart failure is rare in GNE myopathy, mild cardiac dysfunction (ejection fraction 46.1%) was observed. Furthermore, respiratory dysfunction was noted with a preserved diaphragm.

Objectives/Hypothesis: Robin sequence (RS) consists of associated micrognathia, glossoptosis, and respiratory dysfunction, with or without cleft palate. Studies on how different patient characteristics impact the severity of respiratory dysfunction are scarce and contradictory; this study investigates how different features affect respiratory obstruction severity at diagnosis of RS in controlled analysis. Study Design: Retrospective cohort study that enrolled 71 RS patients under 90 days old who received care in our institution from 2009 to 2020. Methods: The primary outcome, respiratory dysfunction, was categorized into four severity groups and analyzed using a multinomial logistic regression model that considered age, sex, mandible length, cleft palate, syndromic diagnosis, other airway anomalies, and degree of glossoptosis. Results: Mandible length, syndromic diagnosis, and Yellon grade 3 glossoptosis were related to poorer respiratory outcomes (need for respiratory support). In univariate analysis, for each additional 1 mm of mandible length at diagnosis, a mean reduction of 28% in the risk of needing respiratory support was observed (OR = 0.72; 0.58–0.89); syndromic diagnosis and grade 3 glossoptosis also raised the risk (OR = 6.50; 1.59–26.51 and OR = 12.75; 1.03–157.14, respectively). In multivariate analysis, only mandible length significantly maintained its effects (OR = 0.73; 0.56–0.96), a 27% reduction. Conclusions: Mandible length was an independent predictor for more severe respiratory dysfunction in RS patients, with larger mandibles showing protective effects. Syndromic diagnosis and Yellon grade 3 glossoptosis are also likely to be associated with poorer respiratory outcomes, although this was not demonstrated in multivariate analysis. Level of Evidence: 4 Laryngoscope, 131:2811–2816, 2021 [ABSTRACT FROM AUTHOR]

Severe Coronavirus disease 2019 (COVID-19) is characterized by acute respiratory distress syndrome (ARDS) which may lead to long-lasting pulmonary sequelae in the survivors. COVID-19 shares common molecular signatures with interstitial lung diseases (ILDs), including pro-angiogenic and tissue-remodeling mechanisms mediated by vascular endothelial growth factor receptor (VEGF-R), fibroblast growth factor receptor (FGF-R), and platelet-derived growth factor receptor (PDGF-R). Nintedanib mainly targets these factors and is approved for ILDs. Therefore, we administered nintedanib through compassionate use to three patients with COVID-19 pneumonia requiring extra-corporeal membrane-oxygenation (ECMO). Here, we describe our experience in an attempt to explore the role of nintedanib in lung recovery in COVID-19. Three obese patients aged between 42 and 52 years were started on nintedanib due to difficulty in obtaining lung function restoration and weaning from ECMO support following the removal of orotracheal intubation (OTI). Soon after the start of the treatment, systemic inflammation and respiratory function rapidly improved and ECMO support was withdrawn. Serial chest CT scans confirmed the progressive lung amelioration, also reflected by functional tests during follow-up. Nintedanib was well-tolerated by all the three patients at the dosage used for ILDs and continued for 2–3 months based on drug availability. Although caution in interpreting events is required; it is tempting to speculate that nintedanib may have contributed to modulate lung inflammation and remodeling and to sustain lung repair. Altogether, nintedanib appears as a promising agent in patients with severe COVID-19 and delayed respiratory function recovery, for whom molecularly targeted therapies are still lacking. Clinical trials are necessary to confirm our observations.

Background: To assess respiratory function in cervical chronic compressive myelopathy (CCM) patients in pre-operative period, post-operative period and to compare pre-operative status with post-operative status. Aims and Objectives: 1. To assess respiratory function in cervical CCM patients in pre-operative period. 2. To assess respiratory function in cervical CCM patients in post-operative period, following relief of compression. 3. To compare, pre-operative status with post-operative status. Materials and Methods: A prospective study was done in 50 patients with cervical CCM due to either cervical disc disease or ossified posterior longitudinal ligament (OPLL) who were operated. None of the patients included in the study had any clinical signs & symptoms of respiratory dysfunction. Spirometry was performed in pre-operative and postoperative period after 3 months and results were analyzed. Forced vital capacity (FVC), forced expiratory volume in first second (FEV1), ratio of mean FEV1 to FVC (FEVI: FVC%) and peak expiratory flow rate (PEFR) were calculated. Results: Majority of the patients were in their fourth decade of life with male predominance. Thirty-six patients (72%) presented with prolapsed intervertebral disc and 14 patients (28%) had ossified posterior longitudinal ligament (OPLL). Patients were operated depending upon the pathology. The present study showed that there was significant reduction in preoperative FVC, FEV1, PEFR values as compared with predicted values and they showed significant improvement in post-operative period after surgical relief of compression. Conclusion: Significant yet occult respiratory dysfunction in form of impairment of various lung capacities exists in patients with cervical CCM. An objective evaluation of this occult respiratory dysfunction is essential to prognosticate, prevent respiratory complications and to improve post-operative respiratory rehabilitation. Institution of incentive spirometry as a routine in all cervical CCM cases will be of benefit in preventing respiratory complications. [ABSTRACT FROM AUTHOR]